Haemotology of Systemic Disease Flashcards
What could a patient with lymphoma presenting with jaundice, anaemia and raised LDH be due to?
Lymphoma stage 4 with bone marrow +liver involved
Lymphoma with nodes compressing the bile duct plus anaemia of inflammation
Lymphoma with Acquired auto immune haemolytic anaemia
What is something that may be the first presentation of cancer?
Anaemia
What kind of anaemias are associated with cancer?
Iron deficiency
Anaemia of inflammation (ACD)
Leucoerythroblastic anaemia
Haemolytic anaemia
+Secondary polycythaemia (e.g. renal cell cancer/ liver)
Why may iron deficiency anaemia occur in cancer?
Occult blood loss:
- GI cancers (Gastric/ colon)
- Urinary tract cancers (renal cell carcinoma/ bladder cancer)
What are the biochemical findings in IDA?
Reduced ferritin, transferrin sat
Raised TIBC (total iron binding capacity)
Bleeding until proven otherwise
What are 2 unusual cancer blood syndromes?
Leucoerythroblastic anaemia
Acquired haemolytic anaemia
Immune mediated
What is acquired haemolytic anaemia?
Immune mediated
Non Immune; fragmentation (micro-angiopathic haemolytic anaemia)
Why is the first finding of cancer Leucoerythroblastic anaemia and Acquired haemolytic anaemia?
Often associated with an underlying cancer or systemic disease. Because of the frequency of FBC testing it may be the first laboratory abnormality detected.
What is leucoerythroblastic anaemia?
Red and white cell precursor anaemia
with variable degrees of anaemia
What are the blood film features of leucoerythroblastic anaemia?
Teardrop RBCs (+aniso and poikilocytosis)
Nucleated RBCs
Immature myeloid cells
What are the causes of leucoerythroblastic anaemia?
Cancer (Haematopoeitic/ Non haematopoeitic)
Severe infection (Miliary Tb, severe fungal infection - uncommon)
Myelofibrosis (Massive splenomegaly, Dry tap on BM aspirate)
What haematopoeitic and non haematopoietic cancers can cause leucoerythroblastic anaemia?
Haematopoeitic: Leukaemia/ lymphoma/ myeloma
Non- haematopoietic:
Breast, bronchus, prostate
What are the distinguishing features of haemolysis on FBC?
Anaemia (but may be compensated)
Reticulocytosis
Raised BR (unconjugated)
Raised LDH
Reduced haptoglobins
What are the two groups of haemolytic anaemia?
Inherited: Defects of the red cell
Acquired: Defects of the environment in which the Red cell finds herself
What qualities would you expect in inherited anaemia?
- Lab features present
- Ethnic bg
- FH/ PMH
- Pigment gallstones
What are the 3 components of a red cell?
Membrane
Haemoglobin
Enzymes
Which blood malformations affect membrane?
Spherocytosis
Elliptocytosis
Which diseases have haemoglobin malformations?
Sickle cell disease (structural)
Thalassaemia (Quantitative)
What is an enzyme based blood disorder?
G6PD
What are the two types of acquired haemolytic anaemia?
Immune
Non immune
How do you distinguish between immune and non immune acquired haemolytic anaemias?
DAT/ Coombs
What will be found if an autoimmune anaemia is present?
Spherocytes
DAT positive
+/- associated system disorder e.g. lymphoma, SLE, infection due to immune disturbance, AI disease, idiopathic
What is seen on a blood test for immune haemolytic anaemia?
Reticulocytosis
Raised BR (unc)
Raised LDH
+DAT (idiopathic or underlying AI disease/ lymphocytic blood cancer)
What is acquired immune haemolytic anaemia linked to?
Infection (malaria)
Micro-angiopathic Haemolytic anaemia (MAHA)
What are signs of MAHA?
Red cell fragments (microangiopathy)
Low PLT
DIC (fibrin deposition/ degradation)/ bleeding
may be linked to underlying adenocarcinoma
What causes true polycythaemia?
Polycythaemia vera (PV) - clonal myeloproliferative disorder (JAK2 mutation)
Secondary Polycythaemia (Raised EPO)
What are the causes of secondary polycythaemia?
Cancer: HCC, bronchial and renal cancer
Oxygen related: High altitude, hypoxic lung disease, cyanotic heart disease
How can white cells change in systemic disease?
Increase/ decreased
Mature or immature
Cell type
Lineages (red, white, platelets)
What systemic diseases may change white cells?
Inflammatory
> Auto immune
> Infective
Malignant
Genetic
Metabolic
What are the normal types of white cells?
Granulocytes
Monocytes
T lymphocytes
B lymphocytes
NK cells
What are the immature white cells?
Blasts
Promyelocytes
Myelocytes
How do you investigate WCC?
FBC/ blood film
HIgh WBC/ look at lineage/ morphology/ maturity
What causes neutrophilia?
corticosteroids
underlying neoplasia
tissue inflammation (e.g.colitis, pancreatitis)
Pyogenic infection
myeloproliferative/ leukaemic disorders
infection
Which infections cause neutrophilia?
Localised and systemic infections
acute bacterial, fungal, certain viral infections
Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections.
What is reactive neutrophilia?
Presence bands, toxic granulation, and signs of infection/inflammation
What is malignant neutrophilia?
Neutrophilia basophilia plus immature cells myelocytes, and splenomegaly. Suggest a myeloproliferative (CML)
Neutropenia plus Myeloblasts (AML)
When does reactive eosinophilia occur?
Parasitic infestation
allergic diseases e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia.
Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)
Drugs (reaction erythema mutiforme)
Why does chronic eosinophilic leukaemia occur?
Eosinophils part of the “clone”
FIP1L1-PDGFRa Fusion gene
When does monocytosis occur?
Rare but seen in certain chronic infections and primary haematological disorders
TB, brucella, typhoid
Viral; CMV, varicella zoster
sarcoidosis
chronic myelomonocytic leukaemia (MDS)
Summarise the infections where there is elevated levels of each phagocyte
Neutrophils: bacterial
Eosinophils: Parasitic
Basophils: Pox viruses
Monocytes: Chronic (TB/ brucella)
Which inflammatory diseases have raised Neutrophils or Eosinophils?
N: AI disease, Tissue necrosis
E: Allergic (Asthma, atopy, drug)
Which phagocytes are linked to neoplasia?
Neutrophils: all types
Eosinophils: Hodgkins/ NHL
Which phagocytes cause myeloproliferative disorders?
Neut: CML
Baso: CML
Monocytes: CMML
Which phagocytes cause myeloproliferative disorders?
Neut: CML
Baso: CML
Monocytes: CMML
How do you tell if something is secondary or primary?
Secondary (reactive); polyclonal response to infection, chronic inflammation
Primary; monoclonal lymphoid proliferation e.g. CLL, NHL. Is it T or B cell?
How do you interpret a lymphocytosis?
Approach
Clinical
Symptoms suggestive of infection or lymphoma
Massive lymphadenopathy or splenomegaly
FBC
Degree of lymphocytosis
Light microscopy/ morphology
Mature cells or primitive lymphoblasts
Flow cytometry
Lineage; B or T cells
Stage of differentiation
Molecular genetics
Rearranged: T cell receptor or Immunoglobulin gene
What causes reactive lymphocytosis?
- Infection (EBV, CMV, Toxoplasma, viral hepatitis, rubella, herpes infections)
- Autoimmune disorders
- Sarcoidosis
How do you interpret morphology in lymphocytosis?
Mature lymphocytes (PB)
reactive/atypical lymphocytes (IM)
small lymphocytes and smear cells (CLL/NHL)
Immature Lymphoid cells in PB
lymphoblasts (Acute Lymphoblastic Leukaemia)
What is lymphocytosis?
>3.5x109/l
How does flow cytometry work?
Monoclonal antibody conjugated to fluorescent dye
Anti-CD4/blue, CD34/green, CD7/purple
What info can you get from a flow cytometer?
Forward scatter: Size
Side scatter: granularity
Is CD2 expressed on normal T cells?
Yes
What are some primary germline disorders of Factor IX and Erythrocytes?
Germline/inherited (gene mutated):
Factor IX
▪ Deficiency > haemophilia B
▪ Excess > FIX Padua (gene therapy)
Erythrocytes
▪ Deficiency> b globin chain production > b Thalassaemia
▪ excess > VHL gene > Chuvash polycythaemia
What are some secondary disorders of erythrocyte and Factor VIII excess and deficiency?
Erythrocytes
◼ Excess > hypoxia > cyanotic heart disease
◼ Deficiency> anti-RBC antibodies > Immune haemolysis
Factor VIII
◼ Excess > inflammatory response
◼ Deficiency>anti-FVIII auto-antibodies (acquired
haemophilia A)
what are the names of the conditions when there is raised or reduced: soluble factors, erythrocytes, platelets, leucocytes?
Soluble factors:
◼ raised FVIII in Inflammation > Thrombosis risk.
Erythrocytes
◼ Raised {altitude/hypoxia or Epo secreting tumour}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 or Fe}
Shortened survival {Haemolytic anaemia}
Platelets
◼ Raised {Bleeding, Inflammation, splenectomy}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 }
Shortened survival {ITP, TTP}
Leucocytes
◼ Raised {Infection, Inflammation, corticosteroids}
◼ Reduced
BM infiltration or deficiency disease {Vit B12 }
What are some primary acquired haematological diseases of Erythrocytes and Myelocytes?
Somatic/acquired (gene mutated) BM rapid turnover organ!
Erythrocytes
▪ Excess> JAK2 V617F> Polycythaemia vera
Myeloid/granulocytes
▪ BCR-ABL1 > Chroinic myeloid leukaemia
What is the difference in ratio of light chains between reactive and malignant b cells?
60: 40 kappa and lambda
99: 1 kappa or lambda skewed
What investigations can you do in haematology?
>Morphology- blood film/ biopsy- architecture of tumour, cytology, cytochemistry
>Immunophenotype- flow cytometry, immunohistochemistry
>Cytogenetics- conventional karyotyping, fluorescent in-situ hybridisation (FISH), Interphase FISH, Metaphase FISH
>Molecular genetics- mutation detection, direct sequencing, Pyrosequencing, PCR analysis, gene expression profiling, whole genome sequencing
How do you classify the malignant cell and link it to it’s normal cell counterpart?
Primitive lymphoid blast cells expressing B cell marker > B cell Acute lymphoid leukaemia
Mature lymphoid cells expressing T cell antigens and involving skin> cutaneous T cell lymphoma
Mature erythrocytes with JAK2 mutation> polycythaemia vera
What are 2 disorders of soluble protein deficiency?
◼ Factor VIII > Haemophilia A> bleeding
◼ Protein C > pro-thrombotic
What are the disorders of red cell quantity?
Polycythaemia
Anaemia
What are examples of excesses of granulocytes and lymphocytes?
Granulocytes > leukaemia(CML) or reactive eosinophilia
Lymphocytes > leukaemia(CLL) or Lymphopenia (HIV)
What is a disorder of platelets?
Essential thrombocythemia or ITP
What are primary disorders?
Primary disorders arise from DNA mutation(s)
What is a secondary disorder?
Secondary disorders are changes in haematological
parameters 2ndry to a non-haematological disease
